Chediak-Higashi syndrome natural killer cells: a protein kinase C defective activation/regulation defect?
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Biomedical subjects
Publications and source records attributed to B Esparza.
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It is well known that the immune response declines with senescence and it is suggested that these changes render an individual susceptible to infection, autoimmune phenomena and cancer. Bacterial and viral infections are a major cause of illness and death amongst aged subjects, and once infection is established, the elderly also have a diminished capacity to prevent its spread (1). The cellular and molecular basis for this age-related decline in immunocompetence are still unknown and, possibly, are related to an alteration in cell transduction mechanisms (2).
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Infections are major cause of illness and death amongst elderly people. Peripheral blood CD8+ T lymphocytes -which play a crucial role in host defence against viral infections-. are divided in subsets based upon the expression of several cell and activation markers. Since in senescence changes in peripheral blood CD8+ T lymphocyte compartment have been described, studies were performed to determine whether in aging there are variations in the peripheral blood CD8+CD38+, CD8+CD57+, CD8+HLA-DR+, CD8+CD45RA+ and CD8+CD45RO+ cell subset. A decrease in the CD8+CD45RA+ lymphocytes was observed, indicating that variations in the CD8+ compartment can take place with ageing.
Allele and genotype frequencies at the HLA-DQA1 locus were determined in Basque Country populations using PCR methodology and a dot-blot assay with ASO probes. The results showed no deviation from the Hardy-Weinberg equilibrium. No differences were found between the three Basque Provinces, but gene frequencies were significantly different from those of some other Spanish and world populations.
Antibodies to HTLV-I/II were investigated in sera from 7521 individuals living in Spain. They were classified in four major groups: a) subjects at high risk of retroviral infections e.g. parenteral drug addicts, homosexuals, prostitutes, and multiple-transfused individuals; b) patients suffering illness associated with HTLV-I in endemic regions; c) immigrants from endemic areas; and d) blood donors. Sera were collected from 1984 to December 1991. Repeatedly reactive ELISA was found in 211 samples (2.8%), but Western blot only confirmed the presence of HTLV-I/II antibodies in 23 samples (0.30%), corresponding to eight (0.25%) out of 3207 drug abusers, six (0.72%) out of 894 immigrants (five Africans and one South American), three (0.41%) out of 727 patients with HTLV-related diseases (one woman with HTLV-I associated myelopathy had received blood transfusions in an endemic area), four (0.54%) out of 793 prostitutes, one multiple-transfused native woman, and one (0.16%) out of 603 native seamen. The Western blot antibody pattern confirmed HTLV-II infection instead of HTLV-I in nine (39%) subjects. The remaining 14 (61%) HTLV-reactive samples were interpreted as HTLV-I seropositive, most of which were from immigrants. None of 857 blood donors analysed was reactive for HTLV antibody. These results suggest that both HTLV-I and HTLV-II are present in Spain, although at a low rate and mostly restricted to individuals coming from endemic areas, drug addicts, and prostitutes. Furthermore, diseases related to HTLV-I (particularly lymphoproliferative disorders, and subacute myelopathies) seem to be rarely associated with these viruses in Spain, a non-endemic area.
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The epidemiological aspects of the infection by the human immunodeficiency virus, HIV, in the Spanish population as described in the literature are reviewed. From the published studies is evident that HIV infection is limited to the population risk groups established in the epidemiological world reports, heroin addicts, homosexuals, heterosexuals with sexual contacts with infected persons and blood and hemoderivates receptors. The observed frequencies in these risk groups are similar to that described in other countries.
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An analysis of the epidemiology of the human immunodeficiency virus infection in the Basque Country, Spain is presented. The infection by this virus is mainly detected in intravenous drug addicts. In homosexuals the seropositivity frequency detected was moderate, and infection was also detected in sexual partners of drug addicts.
An analysis of the medical pathologies seen in heroin addicts heroin addicts hospitalized in the Provincia de Vizcaya, Basque Country, Spain, from 1982 to 1987, and its possible association to the infection by the human immunodeficiency virus, HIV, is presented. An increasing of hospitalized addicts per year was observed, being infectious diseases the main pathology detected. HIV infection was present in more than 90% of individuals with non opportunistic acquired infections. Significant annual increase in the number of tuberculosis and candida infections was present. The possible association of HIV infection with increased susceptibility to commonly acquired non opportunistic infections is discussed.
A revision of the World current epidemiological aspects of the acquired immunodeficiency syndrome is presented. It was observed that near 70% of all the world cases occurred in the United States of America and 12% in Europe. There is an increase tendency of the number of cases. However, the analysis of the inter-annual percentage increase showed a tendency to stabilization in Europe and in the United States of North America.
Serum samples from 313 asymptomatic intravenous (IV) drug users from Bilbao (Vizcaya, Vasque Country, Spain) were tested for antibodies to HTLV-III/LAV virus, the probable etiologic agent of the acquired immune deficiency syndrome (AIDS). Viral antibodies were assayed by ELISA test. 41.9% of the sera gave positive reactions. No seropositivity was detected among 22 normal blood donors, 58 chronic alcoholics, or 20 members of the Drug Control Center personnel. Virus specific reactions were confirmed by indirect immunofluorescence using an HTLV-III/LAV producer cell line, and by Western blotting. 55% of the ELISA-positive sera were also positive in Western blot assay. No differences in seropositivity by age or sex were observed but it increased with the period of parenteral drug use. Presence of antibody statistically correlated with the frequency of syringe sharing, confirming the transmission of viral infection by blood products. Altered T4/T8 ratios and lower number of T4 positive lymphocytes were detected among HTLV-III/LAV positive drug addicts.
Serum samples from 850 individuals from Venezuela were tested for the presence of antibodies to HTLV-III/LAV virus, the probable etiological agent of acquired immune deficiency syndrome (AIDS). At the time of the study, none of the individuals tested had symptoms indicative of AIDS or related disorders. Viral antibodies were assayed by indirect immunofluorescence (IF) assay, using a chronically infected, HTLV-III/LAV producer cell line CEM/LAV-NIT established in our laboratory. Twenty individuals (2.5%), 8 of them (40%) female, were seropositive by IF and by confirmatory Western blotting and radioimmunoprecipitation assays. The seropositivity rate ranged from 2.4% (11 of 465) in the general healthy population, 4% (2 of 50) among patients with Chagas' disease, and up to 29.2% (7 of 24) among patients with acute malaria infection. The titers of HTLV-III/LAV antibodies ranged from 1:40 to 1:640. In addition, 2 of 36 patients with hemophilia A (5.5%) also had antibodies to HTLV-III/LAV. Two of 7 patients with acute malaria had specific antibodies both to HTLV-III/LAV and HTLV-I, as determined by IF and Western blotting. None of over 169 randomly chosen, healthy blood donors from seven major Venezuelan cities, as well as none of 99 patients with leukemia/lymphoma, had antibodies to HTLV-III/LAV. The presence of specific antibodies among various Venezuelan populations indicates that HTLV-III/LAV, or a closely related cross-reactive virus, is indigenous in Latin American subjects as was previously indicated for tropical populations of central Africa. Isolation and characterization of this virus will help to understand the origin and etiology of AIDS.